Terfenadine, xcex1-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol, is a known antihistaminic agent which is currently available commercially under the name Seldane(copyright) with a recommended dosage of 60 mg B.I.D. (See PHYSICIAN""S DESK REFERENCE, 46th Edition, 1992, pp. 1349-50, Medical Economics Data, a division of Medical Economics Company, Inc., Montvale, N.J. Terfenadine is disclosed in the Carr et al. ""217 patent [U.S. Pat. No. 3,878,217, issued Apr. 15, 1975].
Terfenadine undergoes extensive (99%) first pass metabolism to two primary metabolites, an active acid metabolite and an inactive dealkylated metabolite. The active acid metabolite has been identified as 4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-xcex1,xcex1-dimethyl-benzeneacetic acid. The acid metabolite has been disclosed in the Carr et al. ""129 patent [U.S. Pat. No. 4,254,129, issued Mar. 3, 1981] as an antihistaminic agent having oral activity. Studies investigating the effect of hepatic and renal insufficiency on the metabolism and excretion of terfenadine are incomplete.
Preliminary information indicates that in cases of hepatic impairment, significant concentrations of unchanged terfenadine can be detected with the rate of acid metabolite formation being decreased. In subjects with normal hepatic function, unchanged terfenadine plasma concentrations have not been detected.
Recently, it has been found that patients with impaired hepatic function (alcohol cirrhosis, hepatitis), or on ketokonazole or troleandomycin therapy, or having conditions leading to QT prolongation (e.g., hypokalemia, congenital QT syndrome), may experience cardiac events of QT prolongation and/or ventricular tachycardia at the recommended dose of terfenadine.
Surprisingly, it appears that patients with impaired hepatic function who are receiving terfenadine acid metabolite in sufficient amount so as to provide an antihistaminic effect will not experience cardiac events of QT prolongation and/or ventricular tachycardia.
The present invention relates to a method of providing an antihistaminic effect in a hepatically impaired patient in need thereof comprising administering to said patient an effective antihistaminic amount of a compound of Formula (1) 
wherein
R1 is hydrogen or hydroxy;
R2 is hydrogen;
or R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2;
n is an integer of from 1 to 5;
R3 is xe2x80x94COOH or xe2x80x94COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; each of A and B is hydrogen or hydroxy with the proviso that at least one of A or B is hydrogen;
or a pharmaceutically acceptable salt and individual isomers thereof.